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Biomedical subjects

J N Fink

Publications and source records attributed to J N Fink.

At least 91 records · Page 5Linked to original sources

Computerized tomography in the evaluation of allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a destructive disease of the lung characteristically associated with central bronchiectasis. This study was designed to determine if high-resolution computerized tomography (CT) could be used to define bronchiectasis in patients with suspected disease. Sixteen patients with asthma were studied. All demonstrated immediate cutaneous reactivity to common aeroallergens including Aspergillus fumigatus. Eight patients had clinical and immunologic evidence of ABPA. Six to 12 high-resolution CT sections (1.5 mm) were obtained at 1- to 2-cm intervals from the aortic knob to the dome of the diaphragm. All radiographs were evaluated separately by two readers in a blinded fashion and graded as to the presence and type of bronchial dilatation and bronchial wall thickening. Bronchial dilatation was seen in 41% of lung lobes in the ABPA group compared to 15% in the non-ABPA asthmatic control group. Upper lobe involvement and bronchial wall thickening was common to both groups. The presence of bronchiectasis in the control group may indicate that asthma is a more destructive lung disease than is currently appreciated. High-resolution CT of the chest has been shown in previous studies to have a sensitivity and specificity approaching that of bronchography, and the current findings support its use in the detection of bronchiectasis in patients with asthma suspected of having ABPA.

Adolescent↗

Surgery for sinusitis and aspirin triad.

An 11-year retrospective study was conducted to evaluate the surgical treatment of sinusitis in aspirin-triad patients. Twenty-five patients were selected for surgery when their sinus disease and asthma progressed despite intense medical treatment. Sixteen patients had radiographic evidence of severe ethmoid disease, and their initial surgical procedures were limited (i.e., bilateral intranasal ethmoidectomies). Of these 16 patients, 6 required subsequent surgery for recurrent sinusitis. Nine of the 25 patients had radiographic evidence of severe antral, as well as ethmoid, disease. Their initial surgical procedures were radical, i.e., bilateral Caldwell-Luc operations with intranasal and transantral sphenoethmoidectomies. None of these 9 patients required further surgical treatment for control. This review indicates that if antral and sphenoid disease are detected in association with ethmoid involvement, a radical surgical approach is the operation of choice.

Adolescent↗

Antibody isotype responses in Aspergillus-induced diseases.

The Aspergillus fumigatus-specific immunoglobulin class and subclasses were evaluated in the sera of patients with allergic bronchopulmonary aspergillosis, aspergilloma, patients with asthma and immediate wheal-and-flare skin test reactivity to Aspergillus antigens, and normal controls. A sensitive sandwich enzyme immunoassay using a biotin-avidin amplification system was used to detect the specific antibodies. No difference was demonstrated in the specific antibody levels against A. fumigatus between the normal controls and A. fumigatus skin test-reactive asthmatic subjects except for immunoglobulin IgD and IgG4 isotypes. Allergic bronchopulmonary aspergillosis (ABPA) sera showed significant elevation of A. fumigatus-specific antibodies of all isotypes. On the other hand, aspergilloma sera, when compared with that of asthmatic individuals, showed significant increases of IgA, IgG1, IgG2, and IgG3 antibodies. The specific antibodies belonging to both IgG1 and IgG2 subclasses were elevated in ABPA, the former predominant in 40% of cases and the latter in 60%, while in aspergilloma IgG1 was predominant. Among the initially diagnosed ABPA patients, all specific Ig isotypes were considerably elevated when compared with sera from other patients being treated with prednisone or when compared with sera from patients who became asymptomatic after treatment.

Antibodies, Fungal↗

Guidelines for the clinical evaluation of hypersensitivity pneumonitis. Report of the Subcommittee on Hypersensitivity Pneumonitis.

In general, a history of exposure to "moldy" hay, birds, or other incriminated occupational or environmental inhalants in a patient with clinical and radiologic features consistent with HSP should lead to the demonstration of serum precipitins to the suspected antigen and an established diagnosis, confirmed by avoidance of the agent involved. Occasionally, other diagnostic procedures are required. The diagnosis is often difficult in domestic exposures, such as humidification and air conditioning systems. A careful environmental history is essential, and at times the physician must inspect the patient's environment personally. In most cases, the diagnosis is established if (1) the history and physical findings and pulmonary function tests indicate an interstitial lung disease, (2) the x-ray film is consistent, (3) there is exposure to a recognized cause, and (4) there is antibody to that antigen. In other exceptional circumstances, bronchoalveolar lavage may help. Biopsy is rarely needed. Special environmental studies and identification of new antigens require research facilities. Provocation tests are research procedures, not necessary for the diagnosis, and not needed in contested workmen's compensation adjudications.

Alveolitis, Extrinsic Allergic↗

Antibody response to low-molecular-weight antigens of Aspergillus fumigatus in allergic bronchopulmonary aspergillosis.

Sera from patients with allergic bronchopulmonary aspergillosis (ABPA) or aspergilloma and normal sera were analyzed for specific antibodies by Western (immuno-) blotting with Aspergillus fumigatus antigens transferred electrophoretically onto polyvinylidene difluoride membranes. Western blot analysis demonstrated consistent reactivity of low-molecular-weight A. fumigatus antigens against ABPA sera but not against uncomplicated aspergilloma or normal sera. None of these low-molecular-weight components had any lectin-binding activity. Sera from patients with aspergilloma, however, frequently reacted with high-molecular-weight components of A. fumigatus. The majority of these high-molecular-weight antigenic components demonstrated concanavalin A-binding activity. The low-molecular-weight bands were discernible in Western blots with sera from all ABPA patients irrespective of disease activities, such as relapse, flare, or treatment. Antibodies detected by methods such as immunodiffusion or enzyme-linked immunosorbent assays demonstrated total antibody responses to most or all antigenic components, while Western blots demonstrated the reactivities of the individual components with the specific antibodies. Western blot analysis thus provided more information for immunodiagnosis of ABPA than other methods, especially when only crude antigens were available.

Antibodies, Fungal↗

Allergic bronchopulmonary aspergillosis from a contaminated dump site.

The inhalation of Aspergillus fumigatus (Af) spores liberated from a municipal leaf compost site led to the development of allergic bronchopulmonary aspergillosis (ABPA) in a patient living in the area. The patient developed characteristic symptoms of ABPA and demonstrated precipitins against Af antigens in his sera. The potential hazard caused by uncontrolled composting resulting in the dissemination of several allergenic fungi and other microbes is exemplified by this case.

Adult↗

Detection of circulating Aspergillus fumigatus antigen in bone marrow transplant patients.

A competitive inhibition enzyme-linked immunosorbent assay able to detect Aspergillus fumigatus antigenemia at a concentration sensitivity of 68 ng/ml was developed. To test the utility of this assay in the diagnosis of invasive aspergillosis, serum was collected twice weekly from all patients in a bone marrow transplant unit. When analyzed retrospectively, A. fumigatus antigen was detected in three of four patients (75%) with proved invasive aspergillosis at autopsy or biopsy and in a solitary patient with suspected but not proved invasive aspergillosis. No antigen was detected in 17 bone marrow transplant unit patients without proved or suspected invasive aspergillosis or in 16 healthy control subjects. Detection of antigen rose with an increasing number of samples tested. A. fumigatus antibody levels were not helpful in the diagnosis of invasive aspergillosis, although in a few patients antibody levels decreased just before death.

Antibodies, Fungal↗

Immune responses to Aspergillus in cystic fibrosis.

Aspergillus fumigatus (Af) is well recognized in its ability to colonize the respiratory tract in cystic fibrosis (CF). Furthermore, a number of the immune responses of the patient with CF to this organism have been characterized, and the immune inflammatory response to Af may result in allergic bronchopulmonary aspergillosis (ABPA). This study evaluated a series of immunologic parameters in 75 patients with CF in order to characterize more fully the spectrum of immune responses of those patients to Af and to clarify the relationship of those responses to the clinical features of ABPA. The patients could be classified into four groups, depending on the clinical and immunologic findings. Eight (10.7%) of the 75 patients had clinical and laboratory evidence of ABPA, including immediate cutaneous reactivity to Af, eosinophilia, elevated total serum IgE, elevated serum IgE-Af or IgG-Af, and precipitating antibody to Af. Ten (13.3%) patients had these features, except that the total serum IgE level was within the normal range. Forty (53.5%) of the patients had no significant criteria for ABPA but had varying immunologic responses to Af, such as immediate cutaneous reactivity to Af in 25 patients and elevated serum IgE-Af and/or IgG-Af in 19 patients. Seventeen (22.7%) patients had no evidence of an immunologic response, as determined by skin testing and serologic assays. The study demonstrated that the response of patients with CF to Af ranges from clinically apparent ABPA to a possible variant of ABPA, to a nondiagnostic group of features consistent with sensitization to Af or to no characteristic immune response.

Adolescent↗

Immunologic response to Faenia rectivirgula (Micropolyspora faeni) in a dairy farm family.

In the present study, cellular and humoral responses to Faenia rectivirgula antigens were evaluated in seven subjects, members of a family who lived and worked on a dairy farm. Four subjects had clinical features of hypersensitivity pneumonitis after exposure to moldy hay. The other three subjects had no clinical disease in spite of similar exposure. Although serum precipitins were found in most subjects, a biotin-avidin-linked immunosorbent assay revealed high levels of F. rectivirgula-specific antibodies only in the symptomatic subjects. In addition, numerous precipitin arcs were present in the sera of the symptomatic but not the asymptomatic subjects by antigen-antibody crossed immunoelectrophoresis. No clear distinction between symptomatic and asymptomatic subjects could be made on the basis of lymphocyte phenotype studies, and antigen-induced lymphocyte transformation was not detected in any subjects. The results indicate that F. rectivirgula-specific antibody levels as detected by biotin-avidin-linked immunosorbent assay and by the presence of precipitin arcs in crossed immunoelectrophoresis may differentiate symptomatic and asymptomatic farmers.

Actinomycetales Infections↗

Isolation and characterization of a relevant Aspergillus fumigatus antigen with IgG- and IgE-binding activity.

An immunologically relevant antigen fraction was isolated from a cytoplasmic extract of Aspergillus fumigatus mycelium. The fraction was obtained by concanavalin-A affinity chromatography and hydrophobic interaction chromatography. Two protein bands were discernible in polyacrylamide gel electrophoresis while two precipitin peaks were detected in crossed immunoelectrophoresis. When tested against sera from patients with Aspergillus-induced diseases, the fraction showed both IgG and IgE antibody-binding activity. All of the sera studied from patients with allergic bronchopulmonary aspergillosis (ABPA) showed high IgG and IgE antibody titers, while sera from patients with aspergilloma and cystic fibrosis with ABPA demonstrated high IgG titers and only a moderate increase in IgE titers. None of the other groups showed any significant antibody titers against this antigen in their sera. Because of its binding to both IgG and IgE antibodies this fraction was found to be useful in the immunodiagnosis of Aspergillus-induced diseases.

Animals↗

Passive transfer of methacholine sensitivity from man to monkey.

A model of human allergic disease, in which nonhuman primates were infused with serum from allergic humans and challenged with appropriate antigen, was used to determine whether the animals also develop hyperreactive airways characteristic of asthma. Anesthetized monkeys were insufflated with increasing concentrations of methacholine aerosol, and changes in pulmonary function were measured. Airway reactivity as assessed by the dose of methacholine aerosol culminating in apnea was determined after infusion of serum from allergic or nonallergic humans or with heated allergic serum. A comparison of the results indicated that only infusion of unheated serum from allergic humans resulted in an increase in airway reactivity to aerosolized methacholine. These results suggest that a factor in the serum of allergic humans may play a role in the hyperreactivity of airways characteristic of asthma.

Animals↗

An outbreak of recurrent acute and chronic hypersensitivity pneumonitis in office workers.

Three episodes of an acute, flu-like illness, one studied in detail, were associated with manipulations on the central air handling system of an office building in Tennessee in the summer and early fall of 1981. Symptoms were compatible with acute hypersensitivity pneumonitis, although the time of onset revealed a biphasic epidemic curve. Breathing air not supplied through the central air handling system protected against disease. Ill persons had significantly more precipitins to agents cultured from the building than did controls. Symptoms suggestive of chronic hypersensitivity pneumonitis were also found. Chronic disease was associated with the presence of humidifiers at home, asthma, and longer work in the building. Acute disease occurred less frequently in smokers and persons who had previously worked in the building before 1976. Persons with acute disease were more likely to have chronic disease. No single etiologic agent could be identified. Because of difficulties with demonstrating safety for reoccupancy, the building was vacated and remains empty at this time.

Acute Disease↗

Aspergillus fumigatus-specific antibodies in allergic bronchopulmonary aspergillosis and aspergilloma: evidence for a polyclonal antibody response.

Patients with the Aspergillus-induced diseases allergic bronchopulmonary aspergillosis (ABPA), aspergilloma (fungus ball), and Aspergillus skin test-positive asthma were differentiated immunologically by radioimmunoassay based on their total immunoglobulin E (IgE) and Aspergillus fumigatus-specific IgE levels. In this study, a new, highly sensitive biotin-avidin-linked immunosorbent assay was used to evaluate A. fumigatus-specific antibodies of all immunoglobulin classes. Studied populations included 13 patients with ABPA, 12 with aspergilloma, 9 with Aspergillus skin test-positive asthma, and 9 normal individuals without asthma. A. fumigatus-specific antibodies of all classes were elevated in patients with ABPA, variably elevated in those with aspergilloma, and lowest in the other two groups. This assay demonstrated significantly higher specific IgE antibody levels in the ABPA group over those of the other groups, even with 1:1,000 dilutions of the sera. This study demonstrated that ABPA is a disease characterized by a polyclonal antibody response to Aspergillus antigen and not just a response to IgE and IgG antibody classes. The measurement of other antibody classes, particularly IgD and IgA, could enhance the immunodiagnosis of ABPA. The biotin-avidin-linked immunosorbent assay was found to be a highly sensitive assay that can be a clinically useful alternative to radioimmunoassay in the measurement of A. fumigatus-specific antibodies.

Antibodies, Fungal↗

Splenic regulation of the murine pulmonary lymph node response.

Exposure to intratracheal immunization and aerosolization with soluble antigen plus murmayl-dipeptide (MDP) induces the development of plaque-forming cells in the pulmonary draining lymph nodes of two of three inbred mouse strains. Splenectomy before immunization led to a heightened plaque-forming cell response in the two responder mouse strains. Adoptive transfer of spleen cells from one strain exposed to sperm whale myoglobin via the respiratory tract revealed the presence of antigen-specific suppressor cells. These observations suggest that the spleen may play a role in the down-regulation of an immune response elicited in the pulmonary draining lymph nodes by exposure of the respiratory tract to soluble antigens plus MDP.

Animals↗